Dijkmans Anneke Corinne, Zacarías Natalia Veneranda Ortiz, Burggraaf Jacobus, Mouton Johan Willem, Wilms Erik Bert, van Nieuwkoop Cees, Touw Daniel Johannes, Stevens Jasper, Kamerling Ingrid Maria Catharina
Centre for Human Drug Research, Leiden, 2333 CL, The Netherlands.
Department of Medical Microbiology, Albert Schweitzer Hospital, Dordrecht, 3318 AT, The Netherlands.
Antibiotics (Basel). 2017 Oct 31;6(4):24. doi: 10.3390/antibiotics6040024.
Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided.
磷霉素是一种杀菌性、低分子量、广谱抗生素，通过不可逆地抑制细胞壁合成的早期阶段，对包括多重耐药革兰氏阴性菌在内的多种细菌具有假定活性。有证据表明，磷霉素与其他通过不同作用机制发挥作用的抗菌药物联合使用时具有协同效应，从而可减少剂量并降低毒性。磷霉素不与血浆蛋白结合，通过肾脏清除。由于其广泛的组织穿透力，磷霉素可用于治疗中枢神经系统、软组织、骨骼、肺部及脓肿感染。磷霉素氨丁三醇的口服生物利用度<50%；因此，磷霉素氨丁三醇口服给药仅被批准作为3克一次性剂量用于治疗尿路感染。然而，根据已发表的药代动力学参数，已针对几种多剂量方案进行了药代动力学/药效学模拟，这可能会导致磷霉素未来用于治疗多重耐药菌引起的复杂感染。由于目前关于耐药机制的基本药理学信息和知识有限且/或存在争议，迫切需要进一步研究，应避免使用磷霉素单药治疗。
